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Novel surface imprinted magnetic mesoporous silica as artificial antibodies for efficient discovery and catch of candidate nNOS–PSD-95 uncouplers for stroke treatment

Abstract

In search of novel efficient nNOS–PSD-95 (nitric oxide synthase–postsynaptic density protein-95) uncouplers from natural products for stroke treatment, highly selective surface molecular imprinted polymers based on sandwich structured magnetic mesoporous silica (Fe3O4@nSiO2@mSiO2@MIPs, MMS@MIPs) were designed and optimized as artificial antibodies. The resultant polymers exhibited satisfactory adsorbing performance and excellent recyclability, and were successfully utilized as sorbents to catch candidate uncouplers from natural products. Furthermore, biological activity and the functional mechanism of the obtained candidates were investigated in vivo and in vitro. Consequently, Coptisine, Chelerythine and Nitidine chloride presented both potent neuroprotective effects on glutamate-injured PC12 cells as well as uncoupling activity targeting nNOS–PSD-95 in vitro. Simultaneously, they effectively ameliorated neurological deficit and reduced infarct volume of MCAO/R (middle cerebral artery occlusion and reperfusion) rats. Therefore, Coptisine, Chelerythine and Nitidine chloride were considered the most promising nNOS–PSD-95 uncouplers for further preclinical studies of ischemic stroke treatment. Keywords: nNOS–PSD-95 uncouplers, magnetic molecularly imprinted polymers, ischemic stroke, artificial antibodies, natural products

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Publication details

The article was received on 23 Nov 2017, accepted on 04 Feb 2018 and first published on 06 Feb 2018


Article type: Paper
DOI: 10.1039/C7TB03044D
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Novel surface imprinted magnetic mesoporous silica as artificial antibodies for efficient discovery and catch of candidate nNOS–PSD-95 uncouplers for stroke treatment

    J. Huang, C. Sun, D. Yao, C. Wang, L. Zhang, Y. Zhang, L. Chen and C. Yuan, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C7TB03044D

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